Organic chemical compounds, particularly amino acids, vitamins, hydroxy acids, keto acids, nucleosides and nucleotides, are used in human medicine, in the pharmaceutical industry, in cosmetics, in the food industry and in livestock nutrition. Many of these compounds are prepared by the fermentation of strains of coryneform bacteria, especially Corynebacterium glutamicum. These fermentation procedures are continually being improved by measures relating to: fermentation technology (e.g., changes in stirring or the supply of oxygen); the composition of the nutrient medium (e.g., the sugar concentration during the fermentation); the working up of the product formed (e.g., by ion exchange chromatography); or the intrinsic output properties of the microorganism itself.
Methods used for improving the output properties of bacteria may involve mutagenesis, or changes in the selection and choice of mutants. For example, strains may be developed that produce the organic chemical compound and that are resistant to antimetabolites. Methods of recombinant DNA technology have been employed for some years for improving of L-amino acid-producing strains of Corynebacterium glutamicum. A summary of various aspects of the genetics, metabolism and biotechnology of Corynebacterium glutamicum may be found in Pühler ((chief ed.) (J. Biotechnol. 104 (1-3): 1-338 (2003)) and Eggeling, et al. ((editors) Handbook of Corynebacterium Glutamicum, CRC Press, Taylor & Francis Group, Boca Raton (2005)).
Nucleotide sequences of the genes or open reading frames (ORF) of Corynebacterium glutamicum ATCC 13032 form part of the prior art and can be determined, inter alia, from the genomic sequence published by Kalinowski et al. (J. Biotechnol. 104:5-25 (2003), Access No. NC—006958)).
Nucleotide sequences of the genes or open reading frames (ORF) of Corynebacterium glutamicum R also form part of the prior art and can be determined, inter alia, from the genomic sequence published by Yukawa et al. (Microbiol. 153(4):1042-1058 (2007)), Accession No. NC—009342).
The nucleotide sequences of the genes or open reading frames (ORF) of Corynebacterium efficiens likewise form part of the art and can be determined, inter alia, from the genomic sequence published by Nishio, et al. (Genome Res. 13:1572-1579 (2003), Accession No. NC—004369).
In addition, numerous nucleotide sequences of Corynebacterium thermoaminogenes are known.
Despite this plethora of sequence data, there are numerous ORFs for which no clear function has been assignable to date. Glucose or sucrose is mostly used as carbon source for the fermentative preparation of organic chemical compounds with the aid of coryneform bacteria. There is a continuous search for alternative suitable raw materials or raw material mixtures.
It is known that Corynebacterium glutamicum can utilize acetic acid as a carbon source. Investigations on the utilization of mixtures of carbon sources, for example mixtures comprising glucose and one or more of the compounds selected from the group of acetic acid, lactate and fructose are described by Cocaign et al. (Appl. Microbiol. Biotechnol. 40:526-530 (1993)), Dominguez, et al. (Appl. Microbiol. Biotechnol. 47(5):600-603 (1997)), Dominguez, et al. (Eur. J. Biochem. 254(1):96-102. (1998)) and Wendisch, et al. (J. Bacteriol. 182(11):3088-96 (2000)).
U.S. Pat. No. 4,368,266 describes a process for preparing L-glutamic acid by using acetic acid as a carbon source with the aid of coryneform bacteria having a defect in isocitrate lyase.
U.S. Pat. No. 4,728,610 describes a process for preparing L-glutamic acid by using carbohydrates and acetic acid as carbon source with the aid of coryneform bacteria.
Wendisch et al. (J. Bacteriol. 182(11): 3088-96 (2000)) observed a reduced glucose uptake when acetic acid and glucose were metabolized together.